Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery.
Summary of "Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery."
Traumatic brain injury (TBI) is common in young children and adolescents and is associated with long-term disability and mortality. The neuropathologic sequelae that result from juvenile TBI are a complex cascade of events that include edema formation and brain swelling. Brain aquaporin-4 (AQP4) has a key role in edema formation. Thus, development of novel treatments targeting AQP4 to reduce edema could lessen the neuropathologic sequelae. We hypothesized that inhibiting AQP4 expression by injection of small-interfering RNA (siRNA) targeting AQP4 (siAQP4) after juvenile TBI would decrease edema formation, neuroinflammation, neuronal cell death, and improve neurologic outcomes. The siAQP4 or a RNA-induced silencing complex (RISC)-free control siRNA (siGLO) was injected lateral to the trauma site after controlled cortical impact in postnatal day 17 rats. Magnetic resonance imaging, neurologic testing, and immunohistochemistry were performed to assess outcomes. Pups treated with siAQP4 showed acute (3 days after injury) improvements in motor function and in spatial memory at long term (60 days after injury) compared with siGLO-treated animals. These improvements were associated with decreased edema formation, increased microglial activation, decreased blood-brain barrier disruption, reduced astrogliosis and neuronal cell death. The effectiveness of our treatment paradigm was associated with a 30% decrease in AQP4 expression at the injection site.Journal of Cerebral Blood Flow & Metabolism advance online publication, 31 July 2013; doi:10.1038/jcbfm.2013.118.
1] Department of Physiology, Loma Linda University, Loma Linda, California, USA  Department of Pediatrics, Loma Linda University Medical Center, Loma Linda, California, USA.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/23899928
- DOI: http://dx.doi.org/10.1038/jcbfm.2013.118
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Medical and Biotech [MESH] Definitions
Aquaporin 2 is a water-specific channel protein that is expressed in KIDNEY COLLECTING DUCTS. The translocation of aquaporin 2 to the apical PLASMA MEMBRANE is regulated by VASOPRESSIN, and MUTATIONS in AQP2 have been implicated in a variety of kidney disorders including DIABETES INSIPIDUS.
Abrupt reduction in kidney function defined as an absolute increase in serum CREATININE of more than or equal to 0.3. mg/dl, a percentage increase in serum creatinine of more than or equal to 50%, or a reduction in urine output. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.
Aquaporin 4 is the major water-selective channel in the CENTRAL NERVOUS SYSTEM of mammals.
Aquaporin 3 is an aquaglyceroporin that is expressed in the KIDNEY COLLECTING DUCTS and is constitutively localized at the basolateral MEMBRANE.
Aquaporin 6 is an aquaglyceroporin that is found primarily in KIDNEY COLLECTING DUCTS. AQP6 protein functions as an anion-selective channel.